Epigenetic age acceleration mediates the association between smoking and diabetes-related outcomes

Clinical Epigenetics

Table 5 Results of six DNAm markers in mediating the associations between former smokers’ pack-years and four health outcomes

Outcome^a	Total effect	95% confidence interval		p-value	Sample size
FG	0.0046	− 0.0013	0.0106	0.129	2452
HbA_1c	0.0050	− 0.0010	0.0109	0.102	2452
FEV1	− 0.0017	− 0.0084	0.0051	0.629	1563
FVC	− 0.0010	− 0.0065	0.0045	0.726	1563

Outcome	Mediator	Mediation effect^b	95% confidence interval		FDR^c	Proportion mediated^d (%)	Sample size
FG	HannumEAA	0.0002	− 3.0E-05	0.0006	0.264	4.3	2445
HbA_1c		0.0002	− 0.0001	0.0006	0.259	4.0	2445
FEV1		0.0002	− 0.0003	0.0008	0.575	− 11.8	1556
FVC		− 0.0001	− 0.0006	0.0004	0.767	10.0	1556
FG	PhenoEAA	0.0004	− 1.0E-05	0.0010	0.138	8.7	2450
HbA_1c		0.0007	0.0002	0.0013	0.013	14.0	2450
FEV1		− 0.0002	− 0.0010	0.0005	0.767	11.8	1561
FVC		1.0E-05	− 0.0007	0.0007	0.968	− 1.0	1561
FG	GrimEAA	0.0032	0.0018	0.0048	< 0.001	69.6	2448
HbA_1c		0.0038	0.0023	0.0057	< 0.001	76.0	2448
FEV1		0.0001	− 0.0013	0.0014	0.957	− 5.9	1560
FVC		− 0.0004	− 0.0016	0.0006	0.590	40.0	1560
FG	DNAm-based pack-years	0.0020	− 0.0001	0.0042	0.145	43.5	2399
HbA_1c		0.0020	0.0001	0.0040	0.117	40.0	2399
FEV1		0.0006	− 0.0014	0.0028	0.710	− 35.3	1526
FVC		0.0017	0.0001	0.0035	0.108	− 170.0	1526
FG	DNAm PAI-1	0.0013	0.0002	0.0025	0.062	28.3	2452
HbA_1c		0.0012	0.0002	0.0025	0.070	24.0	2452
FEV1		− 0.0003	− 0.0008	0.0001	0.336	17.6	1563
FVC		− 0.0004	− 0.0011	− 4.0E-05	0.101	40.0	1563
FG	DunedinPACE	0.0005	0.0001	0.0012	0.062	10.9	2451
HbA_1c		0.0010	0.0003	0.0018	0.016	20.0	2451
FEV1		0.0001	− 0.0004	0.0006	0.906	− 5.9	1562
FVC		− 0.0002	− 0.0007	0.0002	0.501	20.0	1562

^aBefore mediation analysis, FG and HbA_1c were natural-log transformed and then standardized as z-scores; FEV1 and FVC were standardized as z-scores
^bMediation effect is the effect of X (former smokers’ pack-years) on Y (health outcome) through the mediator (DNAm marker)
^cFDR (false discovery rate) represents the FDR-adjusted p-value. Significant effects with FDR < 0.05 are marked in bold
^dProportion mediated was calculated by dividing the mediation effect by the total effect

ISSN: 1868-7083